The alpha-globin polyC binding proteins (alpha CPs) comprise a widely distributed and highly abundant family of RNA-binding proteins. The complex formed by the interaction of alphaCP with its target RNA has been implicated in various post-transcriptional controls, including mRNA stability and translation. The goal of the proposed research is to define the full spectrum of mRNA targets and roles of alphaCPs in the post-transcriptional controls of gene expression. Aim I will optimize and verify a co-purification approach for the isolation of mRNAs that interact with alpha-CPs in vivo. Aim II will utilize a genome wide screen to identify the sets of mRNAs that associates with specific alphaCP isoforms. Aim III will consist of two parts: (A) the alpha CP binding site(s) within representative numbers of target mRNAs will be mapped and then mutated in order to disrupt the alphaCP-mRNA, which will be followed by (B) studies designed to determine the function(s) of the defined alphaCP-mRNA interaction(s).